The present invention relates to a bone substitute material on the base of natural bones and to a process of production thereof whereby the bones pieces are submitted to a pretreatment for removing the soft parts then to a dealbumination by means of a solution of at least 10% H.sub.2 O.sub.2 or a solution of trypsin and then to a treatment by means of ether. Such a bone substitute material and such a process for the preparation of adequate bone capable of reproduction is described in DE-A-961 654 and known under the name of "Kieler Knochenspan". This heteroplastic bone substitute material is obtained from calves and young bovine in which soluble proteins, grease and humidity are removed by special chemical processes so that finally only the network of the bone remains which is comprised of the collagen base substance of the bone and the mineral component of the bone material. This bone substitute material could not fulfill the expectations required for the orthopedic-surgical practice and extensive histological investigations have shown that although at the surface of this bone substitute material a bone deposit partially occurs the latter is obviously hindered by certain foreign body reactions which are due to the still remaining foreign collagen.
In the last two centuries the use of endoprothetics employing alloplastic for the body compatible foreign material and made from metals, plastics and bone cement has strongly increased due to the fact that relatively rapid and good results in the domain of articulation can be achieved which could not be achieved by transplantations of bone parts of natural origin. However, these technical products of substitution are also subjected to wear during use, involve considerable anchoring problems and are not capable of natural regeneration, all of which limits their field. This is particularly true in the domain of the diaphysis where prothetic bridges have not proved successful so that they only serve if necessary as palliative measures for patients with malignant bone tumors and a short life expectation.
The ideal function of a bone substitute is always, when possible, to give rise to regeneration with natural, vital, adaptable bone structures, more particularly for young people having a long life expectation. This purpose cannot be fulfilled with the endoprothetic, however valuable its possibilities are.
In the last two years artisians have tended to produce bone substitute material from synthetic calcium phosphates or hydroxylapatite. This material has the advantage of form stability and so may serve as a matrix for the regeneration of bone. However this matrix cannot be loaded very much. In cases of cross-sectional bone defects it is therefore necessary to execute an additional supporting osteosynthese, normally by means of a metallic plate bridging the remaining blunt ends in a similar way as indicated above with respect of the desired "Kieler Knochenspan". The advantage of the latter is that the synthetic apatite ceramic does not contain immunogenic albumin component. On the other hand there exits a disadvantage in that the synthetic apatite ceramic does not closely imitate natural bone structure, more particularly in the combination of corticalis and spongiosa as in the case of the "Kieler Knochenspan" as does natural bone tissue. In order to achieve similar solidity a greater density with smaller porousness is required which in the case of "Kieler Knochenspan" hinders the subsequent development by the growth of the healing tissue and the natural regenerative bone formation.
In order to avoid the barrierlike obstacles which are bounded to the use of bone substitute material on natural base or spongy apatite ceramic, it is now proposed to achieve a bone induction by means of a mixture of synthetic apatite and cleaned collagen fleece whereby the cleaned immunogen free collagen acts principally as distributing support (see EP-A-0 030 583). This bone substitute material shows very good bone regeneration which leads rapidly to the building of a natural spongy bone network and is well adapted to fill up bone cavities and also as position plastics on still existing endogenic bones, for example in the case of fractures, pseudoarthrosis or stiffening operations of the spinal column. However the material is less well adapted to bridge free defect sections as for example those appearing by defect pseudoarthrosis or cross sectional resections of the bone in the case of bone tumors.
With respect to the prior art there exists therefore a need for a form stable bone substitute material for acting as a matrix for bone regeneration, which, in opposition to the known "Kieler Knochenspan" is absolutely free of antigen that is entirely free of organic substances, which corresponds as far as possible to the natural bone structures and which is similar or identical to the natural human bone. Such a material would permit natural regeneration of bone parts or entire bones destroyed by diseases and removed by surgical procedure. Although the preceding described apatite ceramic may achieve bonelike structures, it is still not possible to produce with it genuine natural bone structures provided through a dense, stable cortex with the corresponding small vascular channels (small channels of Volkmann) and natural spongiosa structures and which promote the growth of healing tissue and the regeneration and which show an optimal biological architectonics.
This leads to the problem of submitting natural bone tissue to a total dealbumination and to liberate it also of the collagen substances which still remain in the bony frame work in the manufacturing process according to DE-A-961 654 for the known "Kieler Knochenspan" so that finally there remains only the natural mineral substance in form of the natural bony frame work. Only a clean "mineral bone" with full dealbumination is reliably free of antigen and it cannot release disturbing immunological rejection reactions after implantation. Such a material would also be superior to the synthetic apatite ceramic because the latter "mineral bone" which is derived from natural bone tissue is not a more or less successful imitation in its chemical mineral composition, mineral crystallization and structure arrangement but it corresponds fully to the natural mineral bone structure.
Attempts to realize full dealbumination with chemical maceration procedures have not been successful. Either full dealbumination and therewith immunological liberty could not be achieved or the known processes have produced, for example through additional boiling, a swelling of the collagen fibers with explosion of the internal mineral structure so that the bone splints have lost the mechanical cohesion and crumbled.
Early and repeated attempts has been made to burn and glow out bone material since the year 1895. Nevertheless, these procedures have not led to successful results because it has been found that glowing often carbonize the soft parts and obstructs the small channels of the bones which produces a chemical and mechanical resistance to the penetrating parts of tissue after transplantation. Bones previously boiled in bicarbonat solutions lose their internal cohesion and crumple. Prior glowing of bone pieces took place on a grate using a Bunsen flame for a maximum of 2 hours. Bauermeister, one of the inventors mentioned in the above German patent came to the conclusion that this process has a theoretical but no practical meaning because the resulting splint has no mechanical strength.